Sesquiterpene lactones are a group of secondary plant metabolites consisting of a 15-carbon structure containing an α-methylene-γ-butyrolactone moiety and other additional functional group(s). Over the last two to three decades, these terpenoids have received considerable attention due to the broad spectrum of their biological activities, to the plants which produce them, and most importantly, because of their pharmacological effects in humans. About 4,000 of these terpenoids have been isolated and identified, most of them in Asteraceae (Compositae, sunflower family) (Schmidt, Curr. Org. Chem. 1999, 3, 577–608). Some of these plants have been used for centuries in indigenous medical practices in different cultures worldwide.
Parthenolide (1) is a Germacrane sesquiterpene lactone with a unique structure. It has been isolated from several different species in Asteraceae (Compositae) family. The well-known Feverfew (Tanacetum parthenium) is one of them.

Feverfew has been used to reduce fever and pain and in the treatment of migraine and rheumatoid arthritis (Heptinstall et al., ACS Symposium Series (1998), 691 (Phytomedicines of Europe), 158–175.). The active component is parthenolide (1). Recently, it has been revealed that parthenolide (1) can induce tumor apoptosis by the inhibition of NF-κB activities (Cory et al., Anticancer Research 2002, 22, 3805–9; Cory et al., Anticancer Research 2001, 21, 3807–11; Gelfanov et al., Blood, 2000, 98, 2508–17; Kang et al, Brit. J. Pharmacol. 2002, 135, 1235–44; Song et al., J. Asian. Nat. Prod. Res. 2001, 3, 285–91).
Parthenolide (1) is a lipophilic, neutral lactone with low polarity, and has a low water-solubility. This limits its further development as a therapeutic agent. According to the literature, the α-methylene-γ-butyrolactone moiety in parthenolide (1) appears to be the most important functionality for its anticancer activity (Wen et al, J. Biol. Chem. 2002, 277, 38954–38964) and modification of this part of the molecule may cause loss of biological activity. Unfortunately, derivatives obtained from the modification of parthenolide (1 molecule at the 14-methyl group and at the 1,10-carbon-carbon double bond result in loss of antileukemic activity.